GABAergic and Serotonergic System Mediated Psychoneuropharmacological Activities of Essential Oil from the Leaves of Aegle marmelos: An in vivo and in silico Approach

Aegle marmelos Corr. (Rutaceae) is reported to have a wide range of biological activities and the leaves of this plant are used as a brain tonic traditionally in India. In this study, the psychoneuropharmacological activities of essential oil obtained from the leaves of Aegle marmelos were investigated for the first time and the possible mechanistic pathway involved in these activities was also investigated, along with molecular docking study. The chemical composition of extracted essential oil Aegle marmelos (AMEO) was analyzed by Gas chromatography combined with Mass-spectrometer (GC/MS). D-limonene (46.08 %) and alpha-phellandrene (35.90 %) were characterized as the major constituents. Firstly, the selection of the dose of essential oil was made by calculating the intraperitoneal LD50 value. Then AMEO (25-100 mg/kg, i.p) was investigated for general behavioral, antianxiety, sedative, anti convulsion, antidepressant, and motor coordination activities. The essential oil exhibited significant anxiolytic and antidepressant-like activities at all doses. Whereas, noticeable sedative and anticonvulsant effects were achieved at a high dose of essential oil. In addition, to find out the possible connections of the GABAergic and serotonergic system in these activities, test and positive control groups were pretreated with flumazenil and p-chloro-phenylalanine. The findings of in vivo study indicated that essential oil (EO) activity seems to have occurred via GABAergic and serotonergic pathways. A molecular docking (in silico) study also was accomplished to establish the possible mechanistic pathway involved in in vivo activity and the findings of the in silico study might validate the results of in vivo activity.